TY - JOUR
T1 - Screening a small library of xanthones for antitumor activity and identification of a hit compound which induces apoptosis
AU - Barbosa, João
AU - Lima, Raquel T.
AU - Sousa, Diana
AU - Gomes, Ana Sara
AU - Palmeira, Andreia
AU - Seca, Hugo
AU - Choosang, Kantima
AU - Pakkong, Pannee
AU - Bousbaa, Hassan
AU - Pinto, Madalena M.
AU - Sousa, Emília
AU - Vasconcelos, M. Helena
AU - Pedro, Madalena
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1 HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1 HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1 HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.
AB - Our previous work has described a library of thioxanthones designed to have dual activity as P-glycoprotein modulators and antitumor agents. Some of these compounds had shown a significant cell growth inhibitory activity towards leukemia cell lines, without affecting the growth of non-tumor human fibroblasts. However, their effect in cell lines derived from solid tumors has not been previously studied. The present work aimed at: (i) screening this small series of compounds from an in-house library, for their in vitro cell growth inhibitory activity in human tumor cell lines derived from solid tumors; and (ii) initiate a study of the effect of the most potent compound on apoptosis. The tumor cell growth inhibitory effect of 27 compounds was first analysed in different human tumor cell lines, allowing the identification of a hit compound, TXA1. Its hydrochloride salt TXA1 HCl was then synthesized, to improve solubility and bioavailability. Both TXA1 and TXA1 HCl inhibited the growth of MCF-7, NCI-H460, A375-C5, HeLa, 786-O, Caki-2 and AGS cell lines. The effect of TXA1 HCl in MCF-7 cells was found to be irreversible and was associated, at least in part, with an increase in cellular apoptosis.
KW - Antitumor activity screening
KW - Apoptosis
KW - In vitro cell growth assays
KW - Thioxanthones
UR - http://www.scopus.com/inward/record.url?scp=85000443221&partnerID=8YFLogxK
U2 - 10.3390/molecules21010081
DO - 10.3390/molecules21010081
M3 - Article
C2 - 26771595
AN - SCOPUS:85000443221
SN - 1420-3049
VL - 21
JO - Molecules
JF - Molecules
IS - 1
M1 - 21010081
ER -